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We investigated whether the polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene, which is associated with insulin resistance in non-diabetic subjects and an earlier onset of non-insulin-dependent diabetes mellitus in Pima Indians, was associated with visceral fat obesity and features of the insulin resistance syndrome in Japanese premenopausal obese women. There was no difference between 131 obese women and 256 control subjects (0.23 vs 0.17, p = 0.112) in the frequency of the Arg64 allele. The visceral fat area measured by computerised tomography scan was greater in homozygous Arg64Arg (172 +/- 17 cm2, n = 6) and heterozygous Trp64Arg (178 +/- 47 cm2, n = 48) women than in women homozygous for the Trp64Trp (121 +/- 46 cm2, n = 77) genotype (p &lt; 0.01). This was also reflected by increased total body fat but not by increased body mass index. The association between the Trp64 allele and visceral fat mass by multiple regression analysis, was independent of age, body mass index and total fat mass (p &lt; 0.004). Moreover, homozygous carriers of the Arg64 allele had higher systolic blood pressure, higher fasting and post-load glucose and insulin concentrations, higher cholesterol, and triglyceride and lower HDL-cholesterol concentrations than homozygous carriers of the Trp64 allele. Some of these differences were also observed between heterozygous Trp64Arg and homozygous Trp64Trp genotypes (glucose tolerance, insulin and cholesterol concentration). We conclude that in obese women the beta 3-AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome.

b 3 -adrenergic-receptor polymorphism: a genetic marker for visceral fat obesity and the insulin resistance syndrome